The term "menopausal syndrome" and its various symptoms have been well described in the literature (e.g. see Essentials of Gynecology, E. S. Taylor, Chapt. 33, 4th Ed., Publ. by Lea & Febiger, Phila., Pa. 1969). The usual symptoms consist of a variety of unpleasant and often highly distressing disturbances involving any or all of the systems of the body and result from hormonal imbalance, essentially from a deficiency of estrogens. Many different estrogens have thus been used in medicine for the treatment of menopausal syndrome.
Some symptoms mostly associated with the menopause are disturbances of the autonomic nervous system classified as vasomotor instability. Such symptoms of vasomotor instability in many patients are usually manifested in the form of excessive or inappropriate perspiration often accompanied by hot flashes (or hot flushes), tachycardia, nervousness, fatigue and insomnia and occasionally by irritability and other distressing secondary symptoms.
At present estrogen replacement therapy provides the most specific and effective method of treating the disturbing symptoms of menopause, including the aforementioned vasomotor symptoms. However, the many adverse and potentially dangerous side effects associated with the administration of estrogenic products are becoming increasingly apparent. For example, diethystilbestrol, a once widely used and well established estrogen, has been implicated as possibly being responsible for vaginal cancer and adenosis of the female offspring of pregnant women treated with the compound (Lancet 1975, 1960). Also ethinyl estradiol and mestranol, which represent estrogenic components in current oral contraceptives are now known to be involved in certain serious side effects associated with oral contraceptives including depression, (Nature 243,58 (1973)), hypertension (Am. J. Obstet. Gynecol. 112, 912 (1972), carbohydrate and lipid abnormalities (Lancet 1969, Oct. 11, 783), interference with blood clotting mechanism resulting in thrombosis and stroke (Ann. Intern Med. 72, 111 (1970)), and jaundice (Am. J. Obstet. Gynecol. 119, 165 (1974)). Also, the administration of estrogens to postmenopausal women has been implicated as a cause of endometrial cancer (Science 191, 838 (1976)). Consequently, there is a need for an improved non-estrogenic method of treating those symptoms ascribed to vasomotor instability, particularly in relation to the menopausal syndrome.